rs9061

Positions:

chr2-230212395-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_080424.4(SP110):c.619G>A(p.Glu207Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,612,608 control chromosomes in the GnomAD database, including 9,687 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 742 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8945 hom. )

Consequence

SP110
NM_080424.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.444

Variant links:

Genes affected

SP110 (HGNC:5401): (SP110 nuclear body protein) The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This gene is a member of the SP100/SP140 family of nuclear body proteins and encodes a leukocyte-specific nuclear body component. The protein can function as an activator of gene transcription and may serve as a nuclear hormone receptor coactivator. In addition, it has been suggested that the protein may play a role in ribosome biogenesis and in the induction of myeloid cell differentiation. Alternative splicing has been observed for this gene and three transcript variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Jul 2008]

SP110 links:

SP140 (HGNC:17133): (SP140 nuclear body protein) This gene encodes a member of the SP100 family of proteins, which are share common domains including an N-terminal homogeneously staining region domain followed by a SP100/autoimmune regulator/NucP41/P75/deformed epidermal autoregulatory factor domain, a plant homeobox zinc finger, and a bromodomain. The encoded protein is interferon-inducible and is expressed at high levels in the nuclei of leukocytes. Variants of this gene have been associated with multiple sclerosis, Crohn's disease, and chronic lymphocytic leukemia. Alternative splicing results in multiple variants. [provided by RefSeq, Aug 2016]

SP140 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052110553).

BP6

Variant 2-230212395-C-T is Benign according to our data. Variant chr2-230212395-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 334910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP110	NM_080424.4 linkuse as main transcript	c.619G>A	p.Glu207Lys	missense_variant	5/19	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11 linkuse as main transcript	c.619G>A	p.Glu207Lys	missense_variant	5/19	2	NM_080424.4	ENSP00000258381	P1	Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.0936

AC:

14243

AN:

152122

Hom.:

741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0757

Gnomad AMI

AF:

0.0802

Gnomad AMR

AF:

0.0654

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.0596

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.0966

Gnomad OTH

AF:

0.0975

GnomAD3 exomes

AF:

0.111

AC:

27759

AN:

251134

Hom.:

2021

AF XY:

0.118

AC XY:

16068

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.0756

Gnomad AMR exome

AF:

0.0432

Gnomad ASJ exome

AF:

0.164

Gnomad EAS exome

AF:

0.178

Gnomad SAS exome

AF:

0.236

Gnomad FIN exome

AF:

0.0580

Gnomad NFE exome

AF:

0.0966

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.101

AC:

147593

AN:

1460368

Hom.:

8945

Cov.:

AF XY:

0.106

AC XY:

77078

AN XY:

726556

show subpopulations

Gnomad4 AFR exome

AF:

0.0808

Gnomad4 AMR exome

AF:

0.0475

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.173

Gnomad4 SAS exome

AF:

0.231

Gnomad4 FIN exome

AF:

0.0597

Gnomad4 NFE exome

AF:

0.0909

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.0936

AC:

14257

AN:

152240

Hom.:

742

Cov.:

AF XY:

0.0945

AC XY:

7038

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0762

Gnomad4 AMR

AF:

0.0653

Gnomad4 ASJ

AF:

0.160

Gnomad4 EAS

AF:

0.168

Gnomad4 SAS

AF:

0.237

Gnomad4 FIN

AF:

0.0596

Gnomad4 NFE

AF:

0.0966

Gnomad4 OTH

AF:

0.0970

Alfa

AF:

0.101

Hom.:

448

Bravo

AF:

0.0899

TwinsUK

AF:

0.0930

AC:

345

ALSPAC

AF:

0.0851

AC:

328

ESP6500AA

AF:

0.0776

AC:

342

ESP6500EA

AF:

0.0938

AC:

807

ExAC

AF:

0.114

AC:

13871

Asia WGS

AF:

0.168

AC:

584

AN:

3478

EpiCase

AF:

0.0975

EpiControl

AF:

0.0985

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.2

DANN

Benign

0.60

DEOGEN2

Benign

0.0014

.;T;T;.;.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.70

T;T;T;T;T;T

MetaRNN

Benign

0.0052

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.69

N;N;.;N;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.69

N;N;N;N;N;N

REVEL

Benign

0.053

Sift

Benign

0.20

T;T;T;T;T;T

Sift4G

Benign

0.34

T;T;T;T;T;.

Polyphen

0.049

B;B;B;.;.;.

Vest4

0.16

MPC

0.34

ClinPred

0.010

GERP RS

-4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over